Bayer Receives U.S. FDA Approval for Xofigo® (radium Ra 223 dichloride) Injection as a New Treatment for Castration-Resistant Prostate Cancer with Bone Metastases

WAYNE, N.J., May 15, 2013 /PRNewswire/ -- Intended for U.S. Media Only -- Bayer HealthCare announced today that the U.S. Food and Drug Administration (FDA) approved Xofigo® (radium Ra 223 dichloride) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease. Xofigo is the first and only alpha particle-emitting radioactive therapeutic agent approved by the FDA that has demonstrated improvement in overall survival (OS) and delay in time to first symptomatic skeletal event (SSE) compared to placebo, as shown in the pivotal Phase III ALSYMPCA trial.1

The commercial production of Xofigo is underway, and first doses are expected to be ready for patient treatment within a few weeks. Bayer has worldwide exclusive marketing rights for Xofigo. Algeta US, LLC and Bayer Healthcare will co-promote the product in the U.S.

"Most men with castration-resistant prostate cancer develop bone metastases, which can decrease overall survival," said Oliver Sartor, MD, North American Principal Investigator for the pivotal trial and medical director of the Tulane Cancer Center. "Xofigo has demonstrated an anti-tumor effect on bone metastases and will be an important addition to the treatment of this cancer."

Bone is the most common site in the body to be affected by metastatic cancer, and bone metastases are particularly prevalent in patients with prostate cancer.3 Approximately 90% of patients with metastatic prostate cancer show evidence of bone metastases.4, 5, 6, 7 Bone metastases can lead to an increase in frequency of skeletal events and are shown to be the main cause of morbidity and death in patients with CRPC.2, 8

"At Bayer, we remain committed to our mission of delivering innovative ways to help patients and physicians, and to bring new treatment options in cancer," said Pamela A. Cyrus, MD, Vice President and Head of U.S. Medical Affairs, Bayer HealthCare Pharmaceuticals. "We are pleased to add Xofigo to our oncology franchise for the treatment of castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases."

Jan Manarite, senior educational facilitator for the Prostate Cancer Research Institute also added, "It is encouraging to have a new treatment for men with castration-resistant prostate cancer who are dealing with bone metastases. Xofigo provides another new option to treat this cancer using a different approach."

Efficacy and Safety Data Supporting Xofigo® (radium Ra 223 dichloride) Approval The approval of Xofigo is based on data from the pivotal Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial. At the interim analysis, Xofigo significantly improved overall survival (OS) [HR=0.695 (95% CI 0.552-0.875), p=0.00185]; median OS was 14.0 months with Xofigo plus best standard of care vs. 11.2 months with placebo plus best standard of care.1 Additionally, at the interim analysis there was a delay in time to first symptomatic skeletal event (SSE) for patients treated with Xofigo vs. placebo.

The most common adverse reactions (greater than or equal to 10%) in patients receiving Xofigo in the ALSYMPCA trial were nausea, diarrhea, vomiting and peripheral edema. The most common hematologic laboratory abnormalities (greater than or equal to 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia and neutropenia.1

About Xofigo® (radium Ra 223 dichloride) Injection Xofigo is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.

Xofigo is an alpha particle-emitting radioactive therapeutic agent with an anti-tumor effect on bone metastases. The active ingredient in Xofigo is the alpha particle-emitting isotope radium-223, which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases. The high linear energy transfer of Xofigo may cause double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium-223 dichloride is less than 100 micrometers which may limit the damage to the surrounding normal tissue.1

In September 2009, Bayer signed an agreement with Algeta ASA (Oslo, Norway) for the development and commercialization of Xofigo. Under the terms of the agreement, Bayer will develop, apply for health authority approvals worldwide and commercialize Xofigo globally.

Important Safety Information for Xofigo® (radium Ra 223 dichloride) Injection Xofigo is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman.

In the randomized trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (less than 1%) was similar for patients treated with Xofigo and placebo. Myelosuppression notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia has been reported in patients treated with Xofigo.

Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be greater than or equal to 1.5 × 109/L, the platelet count greater than or equal to 100 × 109/L, and hemoglobin greater than or equal to 10 g/dL. Prior to subsequent administrations, the ANC should be greater than or equal to 1 × 109/L and the platelet count greater than or equal to 50 × 109/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care.

Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued.

Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations.

The most common adverse reactions (greater than or equal to 10%) in patients receiving Xofigo were nausea, diarrhea, vomiting, and peripheral edema. Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in Xofigo-treated patients (greater than or equal to 10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia.

About the ALSYMPCA Trial The ALSYMPCA trial was a Phase III, randomized, double-blind, placebo-controlled international study of Xofigo with best standard of care vs. placebo with best standard of care in symptomatic CRPC patients with bone metastases. The trial enrolled 921 patients in more than 100 centers in 19 countries. The study treatment consisted of up to six intravenous injections of Xofigo or placebo each separated by an interval of four weeks.

The primary endpoint of the study was overall survival (OS). A key secondary endpoint was time to first symptomatic skeletal event (SSE), as defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention.

About CRPC and Bone Metastases Prostate cancer is the most common cancer among men in the United States (other than skin cancer).9 Approximately 4% of prostate cancer cases are considered distant, which means that the cancer has spread beyond the prostate to distant areas of the body (metastasized).10 If prostate cancer starts to spread to other areas of the body, it most commonly goes to the bone.8

About the Patient Assistance Program Bayer and Algeta offer patient assistance through Xofigo Access Services(SM) which will assist with obtaining coverage and patient support of Xofigo. Patients and providers may contact the program at 1-855-6XOFIGO (1-855-696-3446) for additional information.

About Oncology at Bayer Bayer is committed to delivering science for a betterlife by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now includes three oncology products and several other compounds in various stages of clinical development. Together, these products reflect the company's approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

About Bayer HealthCare Pharmaceuticals Inc. Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of Bayer AG. Bayer HealthCare is one of the world's leading, innovative companies in the healthcare and medical products industry, and combines the activities of the Animal Health, Consumer Care, Medical Care, and Pharmaceuticals divisions. As a specialty pharmaceutical company, Bayer HealthCare provides products for General Medicine, Hematology, Neurology, Oncology and Women's Healthcare. The company's aim is to discover and manufacture products that will improve human health worldwide by diagnosing, preventing and treating diseases.

Bayer® and the Bayer Cross® and Xofigo® are registered trademarks of Bayer. Xofigo Access Services(SM)is a service mark of Bayer.

Forward-Looking StatementThis news release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.